Basophilic Adenoma Research Articles

HIV infection and Cushing's disease

Introduction: People with AIDS can have a dysfunction of the hypothalamic - pituitary-adrenal axis. With regard to HIV infection, most often mentioned is iatrogenic Cushing's syndrome or Pseudo-Cushing's Syndrome. So far there are described only two cases of Cushing disease in HIV -infected persons. Case report: A 48-year-old patient, after eleven years of HIV infection and a year since the introduction of HAART, was diagnosed with Cushing's disease based on cushingoid habitus, lack of suppression of cortisol in screening, elevated ACTH and pituitary tumor. She had transfenoidal surgery and histopathologic findings corresponded to basophilic adenoma. After the operation, short time on hydrocortisone substitution, she generally felt well with regular ART. Four years later, again easily bruising, facial redness, oily skin with acne, weight gain, uneven distribution of stomach adipose tissue, sweating, oligomenorrhea and high blood pressure. There was no rest/relapse of tumor on control pituitary MRI. Initially, elevated ACTH, valid cortisol in daily profiles, later the absence of the suppression of cortisol after 4 mg (LDST) and 8 mg (HDST) of dexamethasone along with maintenance of higher ACTH, indicate recurrence of clinical and laboratory relapse wherefore ketoconazole was introduced. Despite increasing doses of ketoconazole, she held slightly higher morning cortisol, ACTH and with persisting Cushing's syndrome. Conclusion: The coexistence of the two entities could lead to overlapping metabolic and phenotypic characteristics and the interaction between and/or synergism.

Harvey Cushing: Cushing's Disease

In 1932 Harvey Cushing published an article entitled 'Basophil adenomas of the pituitary and their clinical manifestations'. These are rare tumours of the anterior pituitary gland, at the base of the brain, with striking manifestations, which include adiposity of the face and trunk, but not the limbs, weakness, fatigue, abdominal striae, facial hair, high blood pressure and raised blood sugar. Although I spent two years in an army neurosurgical unit, I never saw a case. More frequently, the same clinical picture is produced by a benign adenoma of the suprarenal cortex, but today by far the commonest cause of this condition is seen in the patient receiving high dosage of cortisone, when we talk about the person exhibiting 'Cushingoid features'. Most readers of this journal will have seen such cases.

The history of pituitary surgery for Cushing disease

Although he never performed a pituitary operation for the disease, Harvey Cushing was the first to describe and treat patients with Cushing disease (CD). Other surgeons at the time were reluctant to operate on the pituitary due to the normal sella on skull radiographs in CD and the unclear etiology of the disorder. To better define and understand factors influencing the history of pituitary surgery for CD, the authors analyzed historical texts related to CD biology, diagnosis, and treatment. Cushing's monograph on basophilic pituitary adenomas and cortisol excess appeared in 1932. One year later in 1933, Alfred Pattison performed the first successful pituitary operation for CD by implanting radon seeds in the sella. Resection of a pituitary adenoma for CD was attempted 1 month later in 1933 by Howard Naffziger, resulting in only transient improvement that corresponded to the lack of tumor in the resected tissue. Soon thereafter, Susman in 1935 and Costello in 1936 described pituitary basophilic adenomas at autopsy in patients without premorbid endocrinopathy. They concluded that the adrenal gland was the cause of CD, which resulted in a 3-decade abandonment of pituitary surgery for CD. Jules Hardy in 1963 used the operating microscope to perform the first selective removal of an adrenocorticotropic hormone (ACTH)-secreting microadenoma, which established a pituitary cause and defined the modern treatment of CD. Subsequent reports by Hardy, Laws, and Wilson resulted in widespread acceptance of pituitary surgery for CD. Initial reluctance to operate on the pituitary for CD was multifaceted and included general uncertainty surrounding the etiology of Cushing syndrome as well as a lack of early surgical success, both due to the small size of ACTH-secreting adenomas. Selective removal of ACTH-secreting adenomas identified the source of CD and ended the delay in acceptance of pituitary surgery for CD.

Re-evaluation of the kidney tumors and renal histopathology occurring in a 2-year rat carcinogenicity bioassay of quercetin

Renal histopathology in the most recent 2-year carcinogenicity bioassay of quercetin, in Fischer 344 rats, was re-evaluated in an attempt to determine a mode of action underlying a small increase in renal tubule tumors reported in the males ( NTP, 1992). The re-evaluation confirmed the reported increase in renal tumors in mid- and high-dose males, including a single carcinoma in a high-dose male, as well as an exacerbation of spontaneous, chronic progressive nephropathy (CPN) in male rats only. The re-evaluation also showed that there were no cellular alterations in the kidney indicative of chemical toxicity at 6 months, 15 months, or 2 years. The evidence linked the occurrence of the predominant basophilic adenomas and foci of atypical tubule hyperplasia (ATH) with the exacerbation of CPN to advanced grades of severity, supporting a mode of action involving quercetin interaction with CPN. This mode of action represents a secondary mechanism for renal tumor development, with no relevance for extrapolation to humans. In addition, the single carcinoma present in the high-dose males, along with 4 other lesions ranging from ATH to adenoma in male and female groups, were considered to have a unique phenotype associated previously with neoplasms of spontaneous and familial origin.

Cushing's case XLV: Minnie G.

A 23-year-old patient who was examined in 1910 by Harvey Cushing triggered his lifelong interest in the syndrome that bears his name. "Minnie G.," as she became historically known, presented with a "...syndrome of painful obesity, hypertrichosis, and amenorrhea with overdevelopment of secondary sexual characteristics accompanying a low grade of hydrocephalus and increased cerebral tension." This case stimulated Harvey Cushing's inquisitive mind and sparked an interest that 20 years later culminated in his seminal report, "The basophil adenomas of the pituitary gland and their clinical manifestations (pituitary basophilism)." In this classic work, Cushing reported in detail the cases of two patients encountered from his own practice and 10 similar cases collected from the literature. Minnie G. was the first case that Cushing reported. The clinical course of that case is briefly reviewed in this article.

An ultrarapid prognostic index in microprolactinoma surgery.

Prolactinomas account for approximately 40% of pituitary tumors. If the tumor does not exceed 10 mm at its largest diameter (microprolactinoma), the chances of definitive cure as a result of surgery alone vary from 62 to 89% depending on the series. Until now, however, there was no mechanism to predict whether total excision of a tumor had been accomplished. To improve the chances of total excision, we compared the peri- and postoperative kinetics of circulating prolactin (PRL) in patients judged to be cured and those not cured. The pre-, peri-, and postoperative variations in blood PRL concentrations were determined using assays conducted at 10-minute intervals. Of the 36 patients included in the study, 27 were considered cured (resumption of a normal menstrual cycle within 6 months, PRL concentration at 9 days [mean +/- standard deviation 2.5+/-2.1 ng/ml] and 12 months [4.5+/-2.2 ng/ml] after the operation < 10 ng/ml and normally stimulated by metoclopramide and thyrotropin-releasing hormone [TRH]). Nine patients were not cured (PRL 20+/-15.7 ng/ml at 9 days after surgery, with no response to metoclopramide and TRH). The kinetics of PRL decrease in definitively cured patients were characterized by the following: 1) the initial slope of the curve decreased by at least 11% within the first 10 minutes after resection, and 2) immediate postoperative PRL concentrations were 20 ng/ml or less. The measurement of the kinetics of PRL decrease during surgery allows the chance of gross-total resection to be successfully predicted less than 25 minutes after excision of the adenoma. Provided an ultrarapid assay is available (the test used in the present study took < 15 minutes), this prognostic index would be useful to make a decision to continue the surgical procedure when the initial PRL slope is judged to be insufficient. Its use may also be extended to other pituitary tumors such as somatotropic adenoma and basophilic adenoma (Cushing's disease).

Localisation of a tumor-associated phenotype of benz-aldehyde dehydrogenase in liver carcinogenesis of flounder by quantitative histochemistry

Aldehyde dehydrogenases (ALDHs) oxidize endogeneous reactive aldehydes including lipid peroxidation products (propionaldehyde, malondialdehyde) and are also inducible by xenobiotics like DDT and TCDD. ALDHs are found in injured livers and cancers of contaminant-exposed flounder (Platichthys flesus L.) and showed identical characteristics as in hepatocellular carcinomas of rats by its cytosolic localisation, the preferential oxidation of aromatic compounds (benzaldehyde), dependency on NADP as coenzyme and sensitivity to the specific inhibitor disulfiram. Image analysis showed increased activity of NADP-dependent benzaldehyde dehydrogenase localised in a few cells of early eosinophilic foci and in basophilic adenomas, carcinomas and their invasively growing protrusions (satellites). Disulfiram sensitivity to differentiate between the xenobiotic-inducible isozyme and the tumor-specific isozyme in rats was highest in the early stages of carcinogenesis in the liver of fish. Moderate disulfiram inhibition was observed in non-neoplastic and extrafocal tissue. In neoplastic livers of flounder from contaminated areas (Elbe estuary), hepatocytes in early stages of carcinogenesis were best protected against accumulation of toxic aldehydes by increased activity of the specific tumor-associated isozyme.

Quantitative relationship between transforming growth factor-alpha and hepatic focal phenotype and progression in female mouse liver.

Modulations in the positive hepatocyte growth factor, transforming growth factor-alpha (TGF-alpha) and its receptor epidermal growth factor receptor (EGFR), occur in rat and human liver tumors. The purpose of this study was to determine if TGF-alpha and EGFR are altered in basophilic and acidophilic preneoplastic and neoplastic liver lesions generated in DEN-initiated mice exposed to a variety of hepatocarcinogens. Female B6C3F1 mice were initiated with N-nitrosodiethylamine (DEN) and treated with hepatocarcinogenic concentrations of unleaded gasoline vapor (2,000 ppm), methyl tertiary butyl ether vapor (7,814 ppm), phenobarbital (500 ppm, diet), or chlordane (25 ppm, diet). Hepatic foci and tumors were identified and evaluated immunohistochemically with antibodies for TGF-alpha and EGFR. In all treatment groups, basophilic hepatic foci were negative for TGF-alpha immunoreactivity (554/564, 98%). In contrast, regardless of treatment, acidophilic hepatic foci were immunoreactive for TGF-alpha (107/108, 99%). There was no significant difference in mean hepatic labeling index as measured by the incorporation of 5-bromo-2'-deoxyuridine between foci immunoreactive and nonimmunoreactive for TGF-alpha. The incidence of immunoreactivity for TGF-alpha increased in hepatocellular tumors that were predominantly of the basophilic phenotype. Of basophilic hepatocellular adenomas, 16/81 (20%) were immunoreactive for TGF-alpha, while 17/29 (59%) of hepatocellular carcinomas stained positive for TGF-alpha. A similar increased incidence of EGFR immunoreactivity was found in basophilic hepatocellular adenomas (17/67, 25%) and carcinomas (19/28, 68%) relative to basophilic foci (11/367, 3%), suggesting an autocrine mechanism for the development of mouse liver tumors. The increased incidence of TGF-alpha immunoreactivity in basophilic liver tumors suggests that TGF-alpha is a marker of tumor progression in mouse liver. Furthermore, TGF-alpha modulations were dependent on phenotype rather than treatment, indicating inherent differences in the expression of TGF-alpha in basophilic and acidophilic hepatic lesions.

Transsphenoidal selective adenomectomy is the treatment of choice in patients with Cushing's disease. Considerations concerning preoperative medical treatment and the long-term follow-up.

Cushing’s observation, that most patients with the disease named after him harbor small basophilic pituitary adenomas, has been confirmed by the success of transsphenoidal surgery in the majority of patients. Monoclonality of such tumors supports the concept of a primary pituitary origin of the disease, which indeed then should be cured after their selective removal. It has become evident that ACTH secretion by the normal corticotrophs surrounding these microadenomas is suppressed in most cases and that this suppression persists for many months after the selective removal of ACTH-secreting microadenomas before a gradual normalization occurs. This initial period after surgery is accompanied by clinically evident hypocortisolism to a degree that is seldom achieved more thoroughly after surgery on other types of pituitary tumors. A gradual return to normal of the diurnal rhythm of ACTH and cortisol, of the response to an insulin-induced hypoglycemia, of daily adrenal cortisol production, as well as a return to normal sensitivity of the restored hypothalamopituitary adrenal axis to low dose dexamethasone supports the concept of a real cure in these patients. Most series describing the results of selective removal of ACTH-secreting tumors by transsphenoidal surgery report an overall percentage of immediate remission of about 75%. Amongst the therapeutic failures a small group of patients can be identified in whom the diagnosis of pituitary-dependent Cushing’s disease was wrong after all. This group includes individuals with occult tumors secreting ACTH and/or CRH ectopically, patients with primary glucocorticoid receptor resistance, and patients with secondary autonomous adrenocortical lesions. The majority of therapeutic failures, however, are neurosurgical. Several categories can be recognized: patients in whom extensive pituitary exploration did not reveal an adenoma, patients in whom the tumor could not be completely removed (in many of these cases invasive tumor penetration of bone or surrounding tissue made selective removal technically impossible), and finally an undetermined number of patients with a seemingly discrete lesion that was, in retrospect at microscopical examination, surrounded by hyperplastic corticotrophs. There is no ideal therapy for patients with Cushing’s dis

Transnasal stereotactic surgery of pituitary adenomas concomitant with acromegaly.

Since 1960 we have performed stereotactic transsphenoidal cryohypophysectomy in 70 patients with pituitary adenomas, 42 women and 28 men, aged 11-59 years. The dominant clinical syndrome was acromegaly in 50 patients, galactorrhea in 9, amenorrhea in 5, adiposogenital dystrophy in 4 and gigantism with mild endocrine symptomatology in 2 patients. In 67 patients the histological structure of the tumor was established by biopsy (50 patients with eosinophil adenoma, 10 with mixed-type adenoma, 4 with chromophobe adenoma and 3 with basophil adenoma). Somatotropic hormone, human growth hormone, prolactin, ACTH and 17-ketosteroid levels indicated active/inactive adenomas. In 42 cases the adenoma was only intrasellar, which was confirmed by contrast X-ray investigations, CT scanning, angiography and ophthalmological investigation. Transnasal stereotactic cryohypophysectomy was performed in all 70 cases using a stereotactic apparatus especially designed for operations on the pituitary. All patients (except 2) tolerated the operation well. No complications occurred. Vision deteriorated after operation in 1 patient. Thrombosis of the left middle cerebral artery developed in another patient. All the other patients noted improvement directly after operation - rapid diminution of signs of acromegaly and rapid restoration of normal values in hormonal tests. Six patients with continuing growth of the tumor underwent a second operation 1.5-6 years after the first operation. We conclude from our own clinical experience and information from the literature that transnasal stereotactic cryodestruction is highly effective and relatively safe in the management of pituitary adenoma.

The Basophil Adenomas of the Pituitary Body and Their Clinical Manifestations (Pituitary Basophilism)1

Obesity ResearchVolume 2, Issue 5 p. 486-508 Free Access The Basophil Adenomas of the Pituitary Body and Their Clinical Manifestations (Pituitary Basophilism)† Harvey Cushing M.D., Corresponding Author Harvey Cushing M.D. Professor of Surgery, Harvard Medical SchoolJohns Hopkins University Press, 2715 N. Charles Street, Baltimore, MD 21218-4319.Search for more papers by this author Harvey Cushing M.D., Corresponding Author Harvey Cushing M.D. Professor of Surgery, Harvard Medical SchoolJohns Hopkins University Press, 2715 N. Charles Street, Baltimore, MD 21218-4319.Search for more papers by this author First published: September 1994 https://doi.org/10.1002/j.1550-8528.1994.tb00097.xCitations: 48AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume2, Issue5September 1994Pages 486-508 RelatedInformation

Pathology of preneoplastic and neoplastic renal tubular lesions induced in F-344 rats by sodium barbital, a nongenotoxic renal carcinogen and nephrotoxin.

Sodium barbital (NaBB), a long-duration sedative/hypnotic barbiturate, is a nongenotoxic nephrotoxin and induces chronic persistent increases in rates of cell proliferation in renal cortical tubules of male F-344/NCr rats. In 5 of our 2-stage carcinogenesis experiments with NaBB at doses of 500, 1,000, or 4,000 ppm for periods of up to 106 wk of age, renal tubular cell tumors were found in incidences of up to 25% in rats receiving only NaBB while fewer than 1% of controls had renal epithelial tumors. We reviewed renal tubular proliferative lesions found in these studies and classified the lesions based on morphology, histogenesis, and immunohistochemical findings. Renal dysplastic tubules (DTs; atypical hyperplasia), putative preneoplastic lesions rarely seen in controls, were found in the renal cortex of more than 50% of the NaBB-exposed rats. DTs were classified into grades 1-3, based on lesion size and growth patterns. All renal adenomas were usually of the basophilic phenotype, and 70% of basophilic adenomas displayed solid patterns, while tumors with papillary, cystic, or tubular patterns were seen less commonly. By serial or step sectioning of the DTs and tumors, evidence was found indicating that the high grades (grade 2 or 3) of DTs, some of which arose in the P1 or P2 segment of the proximal tubules, were sometimes connected to the adenomas. Vimentin expression was demonstrated immunohistochemically in NaBB-induced renal tubular adenomas but not in normal tubules. Tumors were usually not immunoreactive for glutathione S-transferase, placental form, but heterogeneous immunoreactivity was also seen in some tumors. Lysozyme was absent in preneoplastic and neoplastic lesions induced by NaBB, while some intact normal proximal convoluted tubules were immunoreactive. The common tumor phenotype induced by NaBB, the basophilic solid adenoma, was similar to the most common type of spontaneous renal tumor found in untreated aging F-344 rats. NaBB may promote naturally occurring renal preneoplastic or neoplastic tubular lesions of this unique phenotype, but it is also possible that it may induce these lesions de novo.

Immunohistochemistry as a predictor of clinical outcome in patients given postoperative radiation for subtotally resected pituitary adenomas.

There is general agreement that postoperative radiation therapy is beneficial for patients with subtotally resected pituitary adenomas. We have identified 41 such patients treated during a 20-year period who received postoperative irradiation for a pituitary adenoma. The usual dose was 5040 cGy in 28 fractions. The mean follow-up time was 10.3 years. On routine hematoxylin and eosin (H&E) staining, there were thirty-three chromophobe, seven eosinophilic, and one basophilic adenoma. Tissue blocks were stained for growth hormone (GH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), prolactin (PRL), and/or adrenocorticotropin (ACTH) using the peroxidase-antiperoxidase immunohistochemistry (IHC) method. Routine H&E staining was a poor predictor of the IHC stain. While most patients with a known clinical endocrine syndrome stained positive on IHC for the suspected offending hormone, many patients without a clinical syndrome also stained positive indicating the presence of hormonally occult adenomas in this locally invasive group. The IHC stain results were compared to clinical outcome. The presence of positive GH IHC staining decreased the 15-year progression-free survival (PFS) from 100% to 64% compared to GH negative adenomas (p = 0.06). There was a trend toward decreased 15-year PFS in patients who did not stain for LH. Positive staining for prolactin, ACTH, or TSH had no influence on the progression-free survival. We conclude that additional prognostic information can be obtained in this subset of patients (by performing IHC analysis) that is not known by the clinical presentation or appearance on H&E stain.

Immunohistochemistry as a predictor of clinical outcome in patients given postoperative radiation for subtotally resected pituitary adenomas

There is general agreement that postoperative radiation therapy is beneficial for patients with subtotally resected pituitary adenomas. We have identified 41 such patients treated during a 20-year period who received postoperative irradiation for a pituitary adenoma. The usual dose was 5040 cGy in 28 fractions. The mean follow-up time was 10.3 years. On routine hematoxylin and eosin (H&E) staining, there were thirty-three chromophobe, seven eosinophilic, and one basophilic adenoma. Tissue blocks were stained for growth hormone (GH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), prolactin (PRL), and/or adrenocorticotropin ACTH) using the peroxidase-antiperoxidase immunohistochemistry (IHC) method. Routine H&E staining was a poor predictor of the IHC stain. While most patients with a known clinical endocrine syndrome stained positive on IHC for the suspected offending hormone, many patients without a clinical syndrome also stained positive indicating the presence of hormonally occult adenomas in this locally invasive group. The IHC stain results were compared to clinical outcome. The presence of positive GH IHC staining decreased the 15-year progression-free survival (PFS) from 100% to 64% compared to GH negative adenomas (p=0.06). There was a trend toward decreased 15-year PFS in patients who did not stain for LH. Positive staining for prolactin, ACTH, or TSH had no influence on the progression-free survival. We conclude that additional prognostic information can be obtained in this subset of patients (by performing IHC analysis) that is not known by the clinical presentation or appearance on H&E stain.

Biochemical microanalysis of pyruvate kinase activity in preneoplastic and neoplastic liver lesions induced in rats by N-nitrosomorpholine

Fundamental aberrations in carbohydrate metabolism have been previously demonstrated in focal hepatic lesions emerging early during hepatocarcinogenesis induced in rat liver by limited oral administration (stop model) of N-nitrosomorpholine. Using this experimental approach, we have now investigated quantitatively the activity of pyruvate kinase (PK), a key enzyme of glycolysis and gluconeogenesis, in individual preneoplastic and neoplastic hepatic lesions, particularly in glycogen storage foci, mixed cell foci, basophilic cell foci, hepatocellular adenomas and carcinomas and in a specific type of preneoplastic hepatic lesion designated as an enzymatically hyperactive focus (EHF). The focal lesions were dissected from freeze-dried tissue sections with a laser microdissection device. This permits the excision of very small foci and the measurement of enzyme activities in serial sections of the same focus with different substrate concentrations, thus enabling possible changes in the isoenzyme pattern to be detected. On average, PK activity was increased in glycogen storage foci. Mixed cell foci showed a nearly normal or slightly decreased enzyme activity. However, a pronounced reduction in PK activity was observed in low glycogen basophilic foci and in basophilic hepatic tumors. An exceptionally high PK activity was found in one glycogenotic adenoma. An increased activity was also observed in EHF. The results suggest that a reduction in PK activity is a relatively late event during the sequence of cellular changes leading from glycogenotic foci to hepatocellular carcinomas. A drastic decrease in the enzyme activity occurs only when low glycogen basophilic cell populations develop from the glycogenotic foci in later stages of hepatocarcinogenesis.

Pituitary Hemorrhage Extending into the Third Ventricle

A case of pituitary apoplexy causing pituitary hemorrhage with extension into the third ventricle is reported. The patient was a 73-year-old, obese female admitted with sudden onset of vomiting and impaired consciousness. Neurological examination revealed that she was stuporous, with marked neck stiffness and a dilated left pupil. A plain skull X-ray showed sellar enlargement and destruction of the dorsum sellae. Computed tomography demonstrated a high-density area in the third and lateral ventricles and a round, high-density mass in the suprasellar cistern. The patient died the next day. Autopsy revealed a large tumor in the sellar and suprasellar areas. The tumor and the hematoma within it compressed the floor of the third ventricle and passed through the lamina terminalis and the hypothalamic region. Histological examination disclosed a basophilic adenoma. The pituitary hemorrhage appeared to be the result of ischemia and necrosis within the pituitary adenoma caused by its acute expansion. The extension of the hematoma into the third ventricle was attributable to the large size of the tumor and its close adhesion to the floor of third ventricle.

Cyclical Cushing's Disease: Two Distinct Rhythms in a Patient with a Basophil Adenoma

A 71-yr-old woman with clinical signs of Cushing's syndrome was studied continuously for an extended period after demonstration of a paradoxical response to dexamethasone. She proved to have a corticotroph cell adenoma of the pituitary which caused secretion of ACTH and cortisol in two distinct rhythms. One rhythm consisted of a period of 40 days of excess cortisol production, followed by a period of 60-70 days of normal production. During the period of excess cortisol production there was a second rhythm, consisting of peaks of cortisol production every 3-6 days with intervening troughs of normal cortisol production. Prolonged clinical remission followed transphenoidal surgery, but the pituitary still has the ability to provoke abnormal amounts of cortisol secretion, as occurred during a postoperative dexamethasone suppression test. The long duration of normal cortisol production phases in this patient demonstrates the difficulty in excluding Cushing's syndrome in patients with suggestive clinical symptoms but normal serum and urinary cortisol levels if these tests are measured for a single short phase of several days.

Results of neurosurgical treatment by a transsphenoidal approach in 10 patients with Nelson's syndrome.

Ten patients with Nelson's syndrome, nine women and one man, aged 22 to 61 years, were treated neurosurgically by a transsphenoidal approach. In four patients, microadenomas were found, ranging in diameter from 4 to 10 mm. Microscopically, mixed adenoma was diagnosed in six cases, basophilic adenoma in three patients, and chromophobe adenoma in one patient. The presence of argyrophilic nerve fibers in the adenoma tissue was noted in one case. The time of observation after transsphenoidal surgery ranged from 6 months to 10 years. Clinical remission was achieved in eight patients; in two of them, radiation therapy was used to complement surgical treatment. In two patients, recurrence of the pituitary neoplasm was observed; anaplasia was revealed at the second operation in one of them. Radiation therapy might be a useful adjunct to neurosurgery in Nelson's syndrome, especially in patients with anaplastic adenoma.

Muscle lesions in hypercorticism

In recent years, there have been many reports in the literature about muscle lesions caused by hypercorticism of both endogenous and exogenous origin. For the first time, muscular disorders in patients with basophilic pituitary adenoma were described in 1932 [15]. Further observations [1a, b, 4, 6, 7, 19, 25] It allowed us to characterize the features of muscular pathology in Itsenko-Cushing's disease and Cushing's syndrome, expressed by muscle weakness mainly of the proximal parts of the legs and pelvic girdle and to a lesser extent of the proximal parts of the arms and shoulder girdle. The muscles of the shins, interosseous muscles of the hands and feet are less often affected. Muscle atrophy does not always reach a significant degree, moreover, it is often masked by excessive fat deposition. Such patients have difficulty climbing stairs, getting out of bed, lifting their arms above the horizontal level. Muscle weakness is combined with a decrease in tendon reflexes until they disappear with severe atrophy. The muscles of the anterior abdominal wall are often affected, which can partially explain the sagging of the abdomen in patients [5].

Transsphenoidal microsurgical management of Cushing's disease. Report of 100 cases.

The development of transsphenoidal microsurgery and the refinement of endocrinological and radiological diagnostic procedures have afforded therapeutic options appropriate to the individual case in patients with hypercortisolism. The present series of 100 cases is derived from 104 patients with the diagnosis of Cushing's disease who underwent transsphenoidal pituitary exploration between 1974 and 1981. Excluding four patients in whom the pituitary gland was not exposed because of intraoperative technical difficulties, an overall cure rate of 78% was achieved. Among 71 patients with tumors confined to the sella turcica, 87% had correction of their hypercortisolism, 11% represented therapeutic failures, and one patient had tumor recurrence. In contrast, among 25 patients with extrasellar extension, correction of hypercortisolism was achieved in only 48%, 40% failed to respond, and 12% of the patients had recurrence. Four patients who failed to respond to total hypophysectomy have ectopic sources of adenocorticotropic hormone. The results indicate that transsphenoidal microsurgical exploration for a basophilic adenoma is the procedure of choice in adults and children with Cushing's disease. The diagnostic and surgical approach to these tumors, as well as pitfalls in the transsphenoidal treatment of Cushing's disease, are discussed.